Minutes of the 106th meeting of the Management …...2019/12/19 · Minutes of the 106th meeting of the Management Board Page 2/25 3inutes from the 105th meeting, held on 3 October

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20 December 2019 EMA/MB/542228/2019 Adopted Management Board

Minutes of the 106th meeting of the Management Board Held in Amsterdam on 18-19 December 2019

The Chair opened the meeting which was held at the Hilton Amsterdam Hotel as the meeting took place during the removal to the new EMA building and the SPARK building was no longer available. She thanked the government of the Netherlands for providing these alternative premises. She welcomed the new members and alternates: Eleftherios Pallis, member for Greece, Anthony Serracino Inglott, member for Malta and Lars Nickel, alternate for Germany.

1. Draft agenda for 18-19 December 2019 meeting

[EMA/MB/547838/2019] The agenda was adopted with no amendments.

2. Declaration of competing interests related to currentagenda

The Secretariat informed members of the Management Board that it had reviewed members’ declared interests in accordance with the Board’s policy on the handling of competing interests. Some potential competing interests relating to the day’s agenda were identified concerning topics B.7 Programming a) Programming 2020-2022, including 2020 work programme, budget, establishment plan b)Draft programming 2021-2023; B.8 Report to the Management Board on the implementation of EU IT systems required by the Clinical Trial Regulation b) Report of the EU Clinical Trial Regulation Coordination group; B.11 HMA-EMA Task Force on the Availability of Medicines, Terms of Reference, Metrics for shortages: Key information for shortage management and monitoring by EU regulators; B.13 Yearly revision of the EMA Information Management Strategy and Information ManagementStrategic Plan; B.15 Electronic product information (ePI): key principles and roadmap; B.19Management of Nitrosamine presence in medicines. The Secretariat informed the board that allconcerned members had been informed before the meeting. Should the need for a vote on the abovetopics arise, the chair would take up the matter again.

Members were asked to declare any specific interests that could not be drawn from their current declaration of interests that could be considered to be prejudicial to their independence with respect to the items on the agenda. No conflicts of interests were declared.

Minutes of the 106th meeting of the Management Board Page 2/25

3. Minutes from the 105th meeting, held on 3 October 2019adopted via written procedure[EMA/MB/542228/2019] The Management Board noted the final minutes, adopted by written procedure on 10 December 2019.

4. EMA Preparedness on Brexit

4.1 Update on EMA Brexit preparednessThe current assumption is that the UK will leave the EU on 31 January 2020. The Withdrawal Agreement (WA) foresees a Transition Period until December 31 December 2020 and MAHs will have until that date to make the necessary changes to ensure that their products continue to comply with EU legislation. EMA Brexit preparedness will continue in other areas, in line with guidance provided by the European Commission’s Task Force for the relations with the UK (UKTF), such as participation of ‘Persons that represent the UK, are appointed or nominated by the UK’ to EMA meetings, and access to databases. An update on EMA’s staffing situation in December provided the availability of higher figures than the best-case scenario presented to the board in October. This is due to a reduction of numbers of staff on long-term leave and to the fact that staff identified as at risk did not leave the Agency between October and December. The anticipated available workforce in January will therefore amount to 776, including a number of staff in pensionable age, commuting or teleworking, or still considered at risk. A new forecast of the staffing situation by the end of 2020 shows a best-case scenario of 786 staff members compared to 749 in the worst-case scenario. Both scenarios include new recruits and provide enough staff to carry out core activities. However even the maximum available workforce under the best-case scenario remains much lower than the staffing levels in London. Other considerations to be made are that 5 Temporary Agents (TA) will be allocated to partly address the resource needs for the implementation of the new veterinary legislation, and that the Commission has requested that the number of 40 Brexit related contract agents is reduced to 35 in 2020. The Agency is now able to replace some staff on long-term leave with interims, but has not yet any experience with the interim agency or Dutch labour law or labour market. Further staff loss is expected to be spread out over the next year, but there may be a peak once staff retention measures phase out. Staff replacement in the best-case scenario will depend on the Agency’s ability to maintain a high recruitment rate and on the availability of the right expertise. The situation is expected to improve over 2020, but the Agency will continue to monitor the situation. The Preliminary Draft Work Programme (PDWP) as agreed by the board in December 2018 has been revised based on the current staff resource status and the trend of increase in staff numbers, taking the current Phase 4 of the Business Continuity Planning (BCP) as a baseline. Prioritisation for the activities to be undertaken is in line with the gradual relaunch of activities in Q3/Q4 2019 agreed at the June 2019 Management Board meeting. Compared to the PDWP, changes have been introduced to add activities not identified in 2018, or to delete activities that have been finalised in 2019 or were not part of BCP Phase 4 and cannot restart due to resource constraints. Due also to activities related to the implementation of new legislation, the Agency is not able to relaunch all the activities that were suspended under BCP Phase 4 and which had been proposed for relaunch in the PDWP 2020. Due to remaining uncertainties on availability of staff in 2020, it was proposed to review staff figures and the WP2020 at the June meeting of the Management Board, also considering the ongoing reviews of activities related to the relaunch of the working parties and clinical data publication, as well as further developments concerning the management of nitrosamine presence in medicines.

The representative of DG SANTE confirmed to the board that it can be expected that by 1 February 2020 the UK will have left the Union and will be covered by the WA. During the transition period the UK will remain in the EU regulatory system but will not be an active member, meaning it will for


example not be able any more to have a Rapporteur role. The representative of the UK reminded the board that the previous UK government saw provisions in the WA for the UK to attend meetings where its presence is necessary and when the results of such meetings would have a direct impact on the UK and not only in the interest of the Union.

4.2 Update on EMA-NL collaboration for relocation to Amsterdam The handover of the EMA building from CGREA to EMA took place as scheduled on 15 November after all the documents had been finalised and signed on time. After the October 2019 board meeting follow-up documents were circulated concerning the permanent EMA building in Amsterdam with two written procedures on 8 and 14 November 2019. An hoc group of Topic Coordinators of the Management Board had reviewed the documents were circulated to the board and concluded that there was no need for further discussion at the board but that they should be circulated for information with a view to ensure full transparency in respect of the Agency’s financial obligations. As announced at the October 2019 Management Board meeting, several quality assurance measures have been taken at the levels of the building consortium, CGREA and EMA. As regards EMA it has availed itself of an external consultant and also conducted an external audit on the lease arrangements for the EMA building. In addition, the Municipality of Amsterdam has been involved in a number of controls on the compliance of the building with the building permit and Dutch legislation and regulations. The external auditor has stated that in their view “the arrangement of the Lease Agreement has been finalised with reasonable assurance regarding the achievement of the business objectives set up by Council decision for moving the Agency from London to Amsterdam and ensuring timely delivery of temporary premises”. Phase 2 of the Delivery Report should be signed off on 6 January allowing EMA staff to start moving into the permanent EMA building as of 13 January 2020 and first meetings to take place. The Agency’s Head of Audit confirmed that the audit on the lease arrangements, which had been requested by the Management Board, had been performed adequately, with the external auditors issuing an overall opinion of the lease agreements being finalised with reasonable assurance and all outstanding issues not posing major problems for preventing the final move into the new building.

5. Update on 30 Churchill Place

A representative of the European Parliament enquired about the legal costs sustained to date by the Agency. These currently amount to ca. € 3 million, but may increase over a 20-year long obligation. The Executive Director expressed his unease over the fact that the Agency finds itself managing real estate in a 3rd country, an activity which is not foreseen under its founding regulation, although the Agency was repeatedly assured during the negotiations with the UK, that its situation would have been taken into account. The subject will be further discussed at the next meeting if needed.


A. Points for automatic adoption/endorsement

A.1 Financial compensation and workload estimation of the EMA organisation of translations of product related information

[EMA/MB/602870/2019; EMA/607478/2019] The Management Board endorsed the increased flat-hourly rate of €46 for 2020.

A.2 Management Board decision – on request for authorisation not to apply Commission Decision C (2019) 4231 final of 12 June 2019

[EMA/MB/461610/2019; Ares (2019)3845058 – 17/06/2019; EMA/461615/2019] The Management Board adopted the decision to request the Commission’s agreement to the non-application of Commission Decision C(2019) 4231 final of 12 June 2019 laying down general implementing provisions on the conduct of administrative inquiries and disciplinary proceedings as it is not suitable to the specific needs of the agencies. EMA will await the adoption by the Commission of an ex ante agreement containing a model decision for adoption by Agencies.

A.3 Corrigendum to the Financial Regulation applicable to the budget of the European Medicines Agency from 1 July 2019

[EMA/MB/598412/2019; EMA/MB/911312/2019] The Management Board adopted a Corrigendum to the Financial Regulation applicable to the budget of the European Medicines Agency from 1 July 2019 to correct a typographical error.

B. Points for discussion

B.1 Highlights of the Executive Director

International Activities

The ICMRA Summit hosted by AIFA took place in Rome and gathered 26 Authorities plus WHO. The Summit focussed on the themes of reliance and international collaboration and addressed various topics, in particular shortages, innovation, digitalised healthcare, clinical trials in neglected populations and pregnant women, and medical use of cannabis. EMA hosted the bilateral meeting between the EU and China NMPA, which took place just before the Rome ICMRA Summit. The ICMRA day, chaired by EMA, saw active discussions on membership and engagement to secure the future of ICMRA. The Executive Director was appointed as a Board member of two organisations closely collaborating with the Agency in the global regulatory environment: CoRe (Duke University) and Multi Regional Clinical Trial (MRCT). Both roles are non-remunerated and will involve two face to face meetings a year. EMA is preparing for the second Instrument for Pre-Accession (IPA), financed by the EU to train accessing and candidate countries on the Acquis Communautaire. The activities will take place over 3 years 2020-2022, with a first training workshop in 2020 at EMA, for which speakers from the Network will be involved. EMA participated in ICH in Singapore, and Japan DIA. Regular teleconferences are held to address the nitrosamine issue with involvement of Health Canada, Japan, FDA, TGA, Singapore and EDQM, and also with Korea and Taiwan in parallel.


EU Activities

On 5 November EMA participated in a second meeting of the other SANTE agencies organised by Anne Bucher (DG SANTE) with the directors to talk about how the EU agencies can contribute to the high-level political priorities of the new EC. The possible use of common IT tools and projects was discussed. On 7 November the Executive Director, together with the Directors of the other ENVI agencies (EFSA, ECHA, ECDC and EEA) was invited by the ENVI committee to introduce the work of the respective agencies to the new MEPs. EMA was asked about the impact of the relocation on its workforce, because MEPs were concerned that EMA might not have sufficient resources to perform all its tasks. The Executive Director was also asked about the impact of the GDPR, as MEPs heard concerns from the research community on the possible consequences for R&D in Europe and on health research in general. The new contact MEP for EMA, Dr Cristian-Silviu Busoi will visit EMA early next year to have a more in-depth discussion about how the Agency can support the ENVI committee in its work.

Organisational changes

Dr Hilmar Hamann joins the European Medicines Agency as the Head of the Information Management Division. Since 2011 he served as the Director for the Office of Business Informatics of the U.S. Food and Drug Administration where he led IT strategy and program management for information technology and business services investments in support of FDA’s human medicines review program.

Update on the European Ombudsman (EO) pre-authorisation inquiry

The European Ombudsman (EO) has issued her final Decision concerning the EMA’s engagement with medicine developers in the pre-submission phase through scientific advice. The EO recognises the value and need for scientific advice (SA) and her suggestions for improvement are in line with EMA’s ongoing initiatives to further increase transparency. EMA has now revised the internal procedural document for rapporteurship appointment to reflect these suggestions and will pursue a model whereby any prior prominent role as coordinator for scientific advice will be recorded and considered during the rapporteur appointment process. With these revised operations the EMA will formally introduce to the greatest extent possible the separation in prominent roles.

First vaccine to protect against Ebola

The CHMP recommended granting a conditional marketing authorisation in the European Union for the first vaccine for active immunisation of individuals at risk of infection with the Ebola virus. This is the result of many years of collaborative global efforts to find and develop new medicines and vaccines against Ebola and will provide among others essential protection for EU healthcare workers operating in high risk areas.

ATMP development

The number of ATMP marketing authorisation applications (MAAs) is increasing, with 2 submitted in the last month and about 10 expected to be submitted in 2020. An estimated total of 25 new MAs are expected by the end of 2021. The number of ATMPs in PRIME is also steadily increasing (45 % of all Prime products are ATMPs). With the accelerating pace of scientific development and the growing expectations of patients and public, ATMP development is now a global activity. An IMI Regulatory Science Summit on ATMPs took place on 3 December 2019 in Brussels. Participants included EMA, FDA, EC, industry representatives, patients and HCP, HTA bodies and NCAs. The Summit discussed potential IMI topics that remain in the non-competitive space, and where regulators see the opportunities for regulatory research questions to be addressed within a public private partnership that could facilitate or unleash development of ATMPs.

Committee Composition


NCAs and EC nominate members and alternates for the EMA scientific committees according to relevant legislation. Since October 2019, EMA includes in the nomination invitation letters the areas of expertise that are currently desirable/needed for the work of the committees based on the current expertise in the committee and expertise needed for upcoming procedures. NCAs are kindly invited to take the desired areas of expertise into consideration when nominating members or alternates.

Staff evolution

The Agency’s ambition to resume as many activities as quickly as possible is dependent on the evolution of its staff. Since leaving London, EMA has lost 140 short term contracts, only partially compensated through the 40 Brexit related Contract Agents (CA) which the Budgetary Authority has agreed to for three years. The loss of these CAs would bring the gap between total available workforce 2017 and 2019 to 134 staff members. For the more stable components of the staff, forecasts are based on the assumption that no additional posts will be received by the Agency between 2020 and 2021 (with the exception of 5 posts for the implementation of the new veterinary regulation). Since 2014 EMA has been subject to a 10% cut in temporary agent posts imposed by the budgetary authority. Furthermore, it needs to be taken into account that over the years the percentage of CA staff has risen, shifting the TA to CA ratio from 4:1 to 3:1 causing higher volatility, knowledge loss, recruitment and retraining costs, as CA turnover is two times higher than the one of TA. In 2020 the Agency will gradually relaunch activities previously suspended, but will be faced with additional workload for activities which were previously un-resourced (carried out by short term staff lost since the move from London) and for which insufficient staff compensation has been received. Among the un-resourced activities which the Agency must carry out because of their public health impact or their legal requirement, many show rising workload trends for 2020, with the creation of a backlog which can only be addressed by using resources from other core areas of the Agency. Regulatory Agencies have to work under strict timelines and to high standards. Despite EMA being largely self-sustained, the Budgetary Authority binds it to rules designed for non-fee earning bodies, therefore EMA cannot match its increasing workload by resourcing it adequately. Even though the fluctuation in workload could be managed, as foreseen by the Legislator, by means of the time limited working contracts foreseen for the agency (TA and CA, no officials) EMA cannot determine and match neither the quantity of its workforce, nor its composition. Should this situation persist, the Agency may not be able to fulfil its mandate.

B.2 Report from the European Commission

New Commission – initial identified priorities

DG SANTE has identified its priorities from the mission letter to Commissioner-Designate Kyriakides: “Ensure that Europe has the supply of affordable medicines to meet its needs and support Member States in improving the quality and sustainability of their health systems”. Focus will be on affordability of medicines, fighting shortages, ensuring future-looking and flexible legislation, ensuring oversight of the global manufacturing supply chain, AMR, communication on vaccination, Cancer Action Plan, and related priorities like European green deal, Europe fit for digital age.

Pharmaceutical Committee – working method and priorities

The European Commission counts on the reactivation of the Pharmaceutical Committee as its advisory body for Commission-led legislative and policy actions. Its agreed working methods allow it to act as a forum between Commission, Member States and EMA, interacting with HMA and open to other external fora. Joint meetings with other expert or stakeholder groups will be possible. Expected output will be delivered as advice on legislative action, guidance or other.

Evaluation of the legislation on medicines for children and rare diseases


The Pharmaceutical Committee has provided help to the Commission in evaluating both Regulations. It was concluded that they have delivered on their objectives and provided new therapies for rare diseases and children, but that there are still considerable unmet needs. Financial incentives do not always provide an adequate solution, and future scientific developments may have an impact on the functioning of the Regulations. A Staff Working Document will be published in spring 2020.

Pharmaceuticals in the Environment

In March 2019 the Commission adopted a Communication on the EU strategic approach to pharmaceuticals in the environment. An ad-hoc Working Group under the Pharmaceuticals Committee is discussing best practices/guidelines in the remit of the Member States.

HTA

The incoming Croatian Presidency will continue to foster technical discussion in Council. The new Health Commissioner-Designate has reiterated her commitment to the HTA proposal.

Mutual recognition agreement EU-US

The 5th Joint Sectoral Committee EU-US took place on 16 December. Auditing of veterinary authorities is progressing well. Once all corrective actions have been taken, recognition of a number of veterinary authorities is expected.

Action plan on the quality of active ingredients: security and oversight of the global supply chain

Following the Valsartan case, and as part of the Pharma Strategy, a number of short term actions have been identified, among which to improve collaboration with China and India, to strengthen the regulatory framework applicable to APIs and implement GMP equivalent to EU standards, as well as to increase Member States third country inspections by a better use of available resources and cooperation with strategic partners. As long-term action the development of standards and guidelines with EDQM and financing of the Joint Audit Programme should be pursued.

Selection process of the EMA Executive Director

A vacancy notice was published in summer and pre-selection interviews were finalised in November. Following a provisional timeline, the pre-selection report with a short-list of pre-selected candidates should be finalised by end of 2019. Following input from the Assessment Centre in January a short-list of candidates should be compiled by the European Commission in February for a possible selection by the EMA Management Board in March. Further required steps are an audition with the European Parliament ENVI Committee in Q2 and the formal appointment by the EMA board before the new Executive Director takes up service on 16 November 2020.

Xavier De Cuyper, Management Board observer to the selection procedure in the pre-selection committee, confirmed the good progress of the procedure to the board, and assured that among the numerous candidates several had a good knowledge of the European medicines agencies regulatory network. The Chair informed the board that should the shortlist not be available in time for the March meeting, a dedicated extraordinary meeting for the nomination would take place in April or May. The exact date could only be made known once the short list becomes available, as documents would need to be circulated three weeks before the meeting. A small group of members will be invited to prepare a standard interview for the candidates.

Members discussed other aspects of the highlights. It was suggested that topics like AMR and environmental impact of medicines which are relevant to deliver the one-health approach should also be discussed at the Veterinary Pharmaceutical Committee or in a joint Committee meeting. A


commitment to a common effort to achieve long term solutions in the oversight of the global manufacturing supply chain was advocated. Finally, the setting of priorities on accessibility, particularly for small Member States was praised. The representative of SG SANTE reassured that the Mutual Recognition Agreement with the US FDA will free up resources and strengthen inspections in 3rd countries. The Pharmaceutical Committee, with support from EPSCO, has started work on accessibility.

B.3 Future-proofing of the EMA

The Executive Director reminded the board of the changes in environment and in the organisation, starting from the loss of short term contracts that cannot be replaced at the time of the relocation, that had led the Agency to carry out internal discussions with high and middle management on how the Agency could respond with a reduced headcount to the new challenges posed by increasing and changing workload. A joint DG SANTE, HMA and EMA meeting on strategy in June further clarified the direction of travel, and was followed over summer by a number of internal meetings leading to the presentation to staff on 15 September and to the Management Board at its meeting of 3 October of a high-level future structure with 9 entities. Since then, a provisional structure of organigramme was designed in October, as the organisation needed to plan the stacking of the new EMA building in time for the move, and resourcing decisions and selection procedures to be launched in November depended on it. The new provisional organisational structure provides opportunities for efficiencies in the current staffing situation, bringing down the number of Divisions from 10 to 7, of Departments from 18 to 13 and of Offices/Services from 70 to 59. Four new Task Forces will deliver mission-critical functions preparing for transformation to tackle new science, new technology and new legislation, and ensuring an interface to the network. An integrated Human medicines Division will better support the network and the quality of the committees’ output. The system is designed to stay flexible to adapt easily to future strategic directions, also in view of the coming change in leadership. The Agency has been communicating with scientific committees and stakeholders during November and December. The transition to the new organisation will occur between January and March 2020 when the new structure will come into effect.

Several members of the board expressed their support for the future-proofing initiative, underlining in particular the potential for improved coordination and scientific support to the committees and for digitalisation in this new landscape, as well as the opportunity to integrate medical devices in the organisation. The representative of DG SANTE stressed the difficult conditions under which the Agency had operated in the last few years, and welcomed the efforts for simplification and streamlining, the succession planning and preparation for the new challenges of regulatory science. There was a request for wider consultation of the board and for more detailed information on how the Agency will function, and some interest was expressed on the cultural component of the reorganisation. The Executive Director replied that the main work in redesigning the organisation had taken place between June and September, while the Agency also had to cope with its BCP, and that it concerned to a great extent a simple internal consolidation and simplification. The four Task Forces however are more outwards facing and it is important to consult stakeholders and the network on their needs. Further discussions, also at the Management Board will take place on how to best serve the network and draw on existing resources. Concerning cultural change, the new organisation will stress matrix work to allow full impact and benefit of change, in particular through the Digital business transformation Task Force. It will be the task of the Regulatory science and innovation Task Force to detect challenges and technological change and prepare the organisation for it.


B.4 Review of activities of the Working Parties of the EMA

[EMA/681159/2019] The Management Board noted the review of activities of the Working Parties (WP) of the EMA carried out by the Review Group. Objectives of the review had been presented to the board at the October meeting when the mandate and the composition of the Review Group was endorsed. Seven high level principles, which had already been presented to HMA in November, were proposed for endorsement by the Management Board along with high level objectives and proposals to be applied the four strategic review areas of governance, architecture design and operations, composition and number of experts/leadership, work planning cycle. Concerning the objective of reorganisation according to the principal domains of Quality, Non-clinical, Methodology and Clinical, the option to add a distinct area for veterinary matters or to include it in under the other four was highlighted. The timeline for the review is ambitious and aims at delivering the proposals by the review group in March to HMA and the Management Board for adoption, in order to allow the reactivation of the Working Parties in the implementation phase. The endorsement of the high-level principles and of the objectives and proposals is necessary in order to carry out the detailed review on an agreed basis. It was noted that the documents had been circulated shortly prior to the meeting as work is ongoing.

Several members expressed appreciation for an extensive work done in a short time and acknowledged its importance for future-proofing the expertise of the WPs and WGs as currently 700 experts attend the WPs, and it is very important that these resources are used effectively. A full review was never carried out in the past, and greater productivity must be achieved through rationalisation and optimisation. The review group assured that it is not the intention of the review to lock experts in static systems, but that it is looking for more agile and flexible ways to deliver guidelines. Some members asked for more time to consider the proposals in depth, and it was agreed to provide comments by written procedure with the deadline of 20 January.

B.5 EMA Regulatory Science Strategy (RSS) to 2025

a) Draft plan and proposals

[EMA/MB/488796/2019] Following a public consultation on the outcome of two stakeholder workshops, one Human and one Veterinary, views and recommendations were analysed in clusters. The top 10 human recommendations and top 6 veterinary recommendations were analysed and further discussed in breakout sessions during two Stakeholder workshops (human 18-19 November and veterinary 5-6 December 2019). The workshop outputs, documents and video recordings of both workshops, were made available on the EMA website. In parallel a qualitative analysis of stakeholders’ views on the RSS will take place to remove any bias and extract concrete actions for further internal and external discussion. In March 2020 the finalised RSS, together with the finalised analysis of the public consultation, will be submitted to the Management Board for endorsement. Implementation of the strategy will be addressed within the 2021-2025 Multiannual Work Programme in the usual EMA planning cycle, with the subsequent cascade to the 2021+ Annual Work Programme, 2021+ Committee Work Plans and 2021+ Working Parties Work Plans. In parallel the RSS will also flow into the EMRN strategy, to be drafted in Q1 and Q2, to be adopted by the Management Board and HMA in September and October after a stakeholder consultation and its follow-up. Finalisation is expected by October 2020.


B.6 Development of European Medicines Regulatory Network (EMRN) Strategy to 2025

The common network strategy to 2025 will be a high-level document including the preliminary six strategic focus areas included in the HMA Concept Paper. It will contain a single overarching introduction, strategic goals and objectives for each of the six strategic focus areas, as well as high level actions identified for later use in the development of work programmes and implementation plans. A Joint EMA/HMA Drafting group was created using similar structures to the HMA drafting groups for the HMA Concept Paper. It is co-chaired by EMA and HMA and is composed of a Coordination Team and the leads of the 6 Theme Teams for the strategic areas. The timeline for the drafting phase foresees that a final draft version for consultations should be available in April 2020 to undergo adoption by written procedure by HMA and the Management Board. Different options for the subsequent stakeholder consultation were discussed in the Steering Group, and the option for a written consultation with a kick-off event on 4 May 2020 to present the draft was chosen over the options for a written consultation only, or over a workshop with targeted stakeholders.

The board welcomed the approach taken. The HMA co-chair of the Coordination Team for the EMRN Strategy reminded the board that further work will be necessary to prepare the HMA Multi Annual Work Plan and to integrate the IT strategy once this is finalised. A representative of patients' organisations praised the attention given to diverse stakeholders during the workshops which he had attended. The representative of DG SANTE welcomed the plan and added that the results of the network strategy will enrich also discussions at the Pharmaceutical Committee.

B.7 Programming

a) Programming 2020-2022, including 2020 work programme, budget, establishment plan

b) Draft programming 2021-2023

[EMA/MB/559448/2019, EMA/MB/533088/2019; EMA/282/2019; EMA/193731/2019] The Management Board adopted the 2020-2022 Programming document and the budget 2020. The Programming document 2020-2023 is presented as a single document and is made up of the Programming 2020-2022, which includes the final 2020 work programme, budget and establishment plan, and the Draft programming 2021-2023. After adoption by the board, the Agency will include any comments received, update the final 2019 figures and divide the documents presented into two separate ones, which will be circulated to the board before being mailed to the European Commission and other institutions by 31 January 2020. The Topic Coordinators Grzegorz Cessak, Catarina Andersson Forsman, Nancy De Briyne and Lorraine Nolan had performed the role of examining the evolving documents on behalf of the board over three months and took part in the presentation.

2020 will be a year still largely based on Phase 4 of the BCP to which other activities, all falling under the same high-ranking category, will be added while the organisation gradually transitions to a ‘new business as usual’ by June 2020. Depending on staff development, an updated Work Programme may be needed in mid-June and will be presented to the board then. In 2020 fee revenue is expected to increase by 3% to € 306.8 million, a smaller than expected growth, but still sufficient to balance the budget. Workload will increase for NCAs and EMA at the same rate as income. Income from EU/EEA contributions will amount to € 51 million of which € 35 million general contribution (including € 2 million to support the implementation of the new veterinary regulation) and € 16 million earmarked for orphan medicines fee reductions. Public health activities in 2020 will be fully fee financed, since


general EU contribution will be consumed by covering Brexit costs. For 2021 a further 4% increase in fee revenue is expected. In many respects the budget for 2020 is still a Brexit budget covering exceptional staff relocation costs, exceptional activities linked to the sub-letting of the London premises and the one-off Dutch financial incentive, the impact of moving to new premises and relaunching activities while moving out of the BCP. The Agency will continue investing in the future of the network and preparing for new legislation while managing limited financial and staff resources. In 2020 the cost of Brexit will go down from € 44.9 million in 2019 to € 40.8 million, mainly due to UK property related costs, but also to staff-related costs. Some exceptional costs will have no impact on the budget, as some costs for fitting out the permanent building and to reduce annual rent over 20 years are covered by the Dutch inducement of € 18 million, and the revenue and expenditure related to the UK property cancel each other out. On the expenditure side, staff costs are down from 2019 due to drop in relocation related allowances, offset partially by lower vacancy rate, training and the contribution for the European Schools. Infrastructure and operating costs go up due to increases in rapporteur payments and delegate reimbursements and other expenses for Scientific Studies, IT projects and the EU NTC. Following the strategical workforce planning, the EMA has requested 836 TA and CA for 2021, up from the currently allocated 822 for 2020. The increases will be offset by the phasing out of the time limited Brexit related CA. Looking at the future when the new financial framework (MFF) comes into effect in 2021, EU budget contribution will start falling sharply. EMA forecasts suggest that this can be absorbed in 2021 by fee revenue increases and lower operating costs in the Netherlands, but there is greater uncertainty from 2022 onwards. For 2021 staffing is requested to increase by 3 of the planned 8 new posts for the new veterinary legislation, 11 TA to tackle the workload, but with a decrease of short-term CA from current 40 to 25. Concerning the Work Programme, Topic Coordinator Grzegorz Cessak welcomed the future-proofing initiative, hoping that EMA can start relaunching activities suspended by the BCP, and highlighted the importance of efficient referral procedures and Pharmacovigilance and epidemiology activities, as well as the recommendations by the HMA-EMA Joint Big Data Task Force. Catarina Andersson Forsman expressed strong support for the Programming Document, which reflects the visions and ambitions of the Agency and the network in a challenging environment. Nancy De Briyne was concerned about EMA having to act in a capacity of landlord and about the trend in decrease of EU budget contribution and its possible consequences on the ability of the Agency to engage in public health activities. The increase in budget and staffing granted for 2020 for the implementation of the new veterinary legislation do not cover future staffing and funding needs, particular for IT systems, and no earmarked funds are foreseen for 2021.

According to the EMA’s IT governance, yearly review and endorsement by the board of the Information Management Strategy and of the Strategic Plan takes place as part of the yearly planning cycle to take into account changes in the environment and priorities. The current proposal was based on the strategic review on how the Agency has delivered in the last year which was marked by the relocation. All activities progressed well, with the large CTIS project now much improved, and projects relating to the implementation of the new veterinary regulation requiring attention, also in terms of resourcing issues. In 2020 the relocation will end, and focus will shift to the development of systems required by legislation, as well as other activities: knowledge transfer and transition to new framework contracts, data centre refresh, regulatory and administrative digitalisation, transition to the new operating model and additional information security capabilities. The changes proposed in the strategy address the need to stabilise the operations of the Agency, renewing its focus post relocation on deferred activities. Information services will be subject to criteria of affordability as well as sustainability. Budget Topic Coordinator Lorraine Nolan contributed with her analysis of the IT budget highlighting the significant drop in investment during the relocation year of 2019. Increases in operational costs and for projects foreseen in 2020 and 2021 might clash with the reality of limits set by staff capacity to deliver on the required programme. An analysis of expenditure shows cost of operations increasing by ca 9% each


year. Investments in dedicated projects to address and contain these increasing maintenance costs would be needed, but there does not appear to be any capacity for them in 2020. Regulatory and administrative digitalisation appear under-resourced, as Telematics consumes a significant percentage of EMA’s IT resources. Unallocated budget capacity for further projects, such as SPOR amounts to only € 0.64 million and is in any case limited by insufficient staff capacity.

The discussion by the board focussed on IT matters. The representative of DG SANTE reminded the Agency that additional funds for € 2 million and 5 FTE allocated to the Agency for 2020 in the conciliation phase during the 2020 budget negotiations, are earmarked exclusively for the implementation of the new veterinary regulation. She added that any request for the draft 2021 budget for resources not previously granted would have little chance of success. Several members objected to the exclusion of SPOR from the 2020 project portfolio and asked for this decision to be reversed or further discussed. Perhaps it could be explored whether Member States could supply resources to help EMA for projects for which only funds are available. The Executive Director was grateful for this suggestion, which is worth considering. He explained that however, as long as EMA is caught up in the loop of high cost maintenance of its obsolescent applications, resourcing of other projects is difficult. Allocating the € 642,000 unallocated funds to SPOR seems a good solution, but it may have difficulties delivering since EMA has experienced staff losses in the domain responsible for SPOR, and what is needed is a significant change of approach. He advocated the potential access to the extensive EU funds which are allocated each year to projects which have no direct impact on the functioning of the EU’s own systems, and expressed hope that not just the European Commission but also the Council will listen to this suggestion. It was agreed to continue the SPOR programme in 2020, and to update the Information Management strategy and strategic plan 2020-2022 to reflect this decision, and to allocate the unallocated IT project budget of € 642,000 to S/PMS to the 2020 project portfolio. The endorsement of the Information Management strategy and strategic plan 2020-2022 will take place by written procedure. See also B.13 Yearly revision of the EMA Information Management Strategy and Information Management Strategic Plan.

B.8 Report to the Management Board on the implementation of EU IT systems required by the Clinical Trial Regulation

The Management Board noted the Update report on the Clinical Trials Information System (CTIS) Project for implementation of the Clinical Trial Regulation, and endorsed the Conclusions of the EU Clinical Trial Regulation Coordination Group (EU CTR CG) on the monitoring of the CTIS project and the plan enabling the audit to start in December 2020.

a) Update on the Clinical Trials Information System (CTIS) Project for implementation of the Clinical Trial Regulation

[EMA/MB/572768/2019-Rev.1; EMA/572767/2019; EXT/671952/2019; EMA/666659/2019] At its meeting of 3 October the Management Board had requested improvement of the quality delivered by the developer, and rationalisation of the critical items needed for audit. Since October the developer delivered Release 11 encompassing 3 sprints. In the release the quality and throughput of items increased in comparison with the previous release. Sprint content adherence and net items have increased, with progress also in the area of regression test results. In October 2019 the Management Board had requested the CT Programme Team to launch an assessment to start the audit by the end of 2020. An Audit Readiness Assessment was prepared and submitted to the board. Starting 14 October 2019 Member States’, the European Commission’s and sponsors’ Product Owners (PO), Member State Rapporteurs, and EMA performed an Operational Assessment on key parts of CTIS in the Sandbox environment. In addition, Technical and Requirement assessments of the system were performed by


EMA with support from the development consortium. Critical items that still need to be fixed/developed for audit were identified and an estimation of the work that needs to be carried out prior to the audit was carried out. Assumptions and preconditions for starting the audit by the end of 2020 were identified. Next steps will be the agreement by Member States POs on the items identified in the Requirement Assessment to be addressed by the audit and two further operational assessments in the first half of 2020 on remaining parts of CTIS to complete the identification of critical items that still need to be fixed/developed for audit, and prioritised within the development capacity available; elaboration of a meaningful audit methodology; definition and agreement of the content and meaning of the Release Validation/User Testing. The development plan for audit and anticipated planning for Go-Live should respect the agreed functional specifications and Product Vision, and should deliver end-to-end functionality in a comprehensive system, enabling users to perform their daily business as required by the Clinical Trial Regulation. Concerning contract transition scenarios for CTIS, the current framework contract expires on 13 July 2020 and can be extended up to one year. The audit version will be delivered under the current developer who will also fix the audit findings. A new framework contract will need to be in place by end of Q4 where a new supplier may be selected. Knowledge transfer to the new supplier will start after the audit. Heads of Agencies were asked to support the approach and to continue providing resources and supporting their POs and Rapporteurs to have time to perform these tasks.

b) Report of the EU Clinical Trial Regulation Coordination group

The chair of the EU CTR Coordination Group presented the group’s report. Improvement of the quality and quantity of delivery has taken place as the developer delivers a considerably higher number of net items than in the previous release, although the results of the regression testing remain stable but below expectations. A reprioritisation exercise (i.e. audit readiness assessment) took place to get a clearer view on the status of CTIS. A project plan up to the audit was agreed. Beginning of June 2020 the functional specifications for the audit will be completely finalised. Any new addition to the list will have to be weighed against the already selected items and if the addition is maintained other items will need to be deprioritised. An overview (heatmap template) of 46 high-level functionalities based on previously prepared documents was developed and adopted. It will be supplemented with further information on the readiness of each functionality as the project advances. There is confidence that the agreed list of issues can be delivered to enable audit start in December 2020. A list of items to be solved in the period between the audit and go-live has already been established but there is still a high degree of uncertainty. It was proposed to endorse the option for a project plan up to the audit to start in December 2020, as well as elaborate action in the Monitoring Subgroup of the EU CTR Coordination Group: continuous monitoring of the KPIs to “to audit” and “to go-live”; elaboration of a process to monitor the delivery of selected items; elaborate a document describing the audit methodology for adoption by the Management Board in March 2020; elaborate a detailed project plan for 2021 in order to fix the go-live of CTIS for endorsement by the board.

A member welcomed the progress achieved with the project, and reminded the board of its duty to maintain a critical perspective on the impact of its development within the portfolio of Telematic projects. The Board endorsed the report of the EU Clinical Trial Regulation Coordination Group “Conclusions of the Coordination Group” and noted the outcome of the assessment on CTIS audit Readiness. It agreed with the plan enabling the audit to start in December 2020, and gave a mandate to the EU CTR Coordination Group, with the support of the Monitoring Subgroup, to continue monitoring the KPIs to audit and Go-Live, elaborate a process to monitor the delivery of the prioritised items, elaborate the audit methodology, and elaborate a project plan covering the activities until Go-Live.


B.9 Mandatory use of the ISO/ICH E2B(R3) format for ADR reporting in the EU

[EMA/MB/567037/2019; EMA/561671/2019] The Management Board confirmed and announced that the use of the ISO Individual Case Safety Report standard as referred to in Article 26(2)(a) of the Commission Implementing Regulation (EU) No 520/2012 and the modalities on how to use this ISO ICSR standard defined in the ICH E2B(R3) documentation, and the ISO terminology on pharmaceutical dose forms and routes of administration referred to in Article 25(1)(f) of Commission Implementing Regulation (EU) No 520/2012, shall become mandatory as of 30 June 2022 in relation to reporting obligations to EudraVigilance. This is based on a PRAC recommendation of 2 October 2019 as regards reporting obligations to EudraVigilance Human. The ISO Individual Case Safety Report (ICSR) format was formally introduced in November 2017 at the time of the go-live of the new EudraVigilance system. In March 2018, ICH agreed to use the ISO IDMP standard terminology for coding of routes of administration/pharmaceutical forms for the ISO/E2B(R3) ICSR format. As this required agreement on a date for use in the EU, a readiness survey was launched end of 2018 with NCAs and pharmaceutical industry associations, resulting in the choice of the June 2022 date.

B.10 HMA-EMA Joint Big Data Taskforce (BDTF) Phase II report

Nikolai Constantin Brun, Chair of the Joint HMA-EMA Task Force on Big Data, joined the meeting for the discussion of this topic.

[EMA/MB/663219/2019; EMA/584203/2019] The Management Board endorsed the BDTF Phase II report and agreed to close the current BDTF and establish an HMA-EMA Big Data Steering Group to take over the recommendations and support the EU Network Strategy to 2025. The Phase I report of the BDTF was endorsed by HMA and EMA in early 2019. In Phase II the 47 Core Recommendations and 138 Reinforcing actions were reallocated across 6 subgroups, business cases for prioritised recommendations were drafted, comments from consultations were analysed and an interim plan was presented to HMA and the Management Board in June 2019. The top-10 priority recommendations were identified and are fully compatible with the current EU legal framework for the regulation of medicinal products: Deliver a sustainable platform to access and analyse healthcare data from across the EU (Data Analysis and Real World Interrogation Network - DARWIN); Establish an EU framework for data quality and representativeness; Enable data discoverability; Develop EU network skills in Big Data; Strengthen EU network processes for Big Data submissions; Build EU network capability to analyse Big Data; Modernise the delivery of expert advice; Ensure data are managed and analysed within a secure and ethical governance framework; Collaborate with international initiatives on Big Data; Create an EU Big Data ‘stakeholder implementation forum’. The network resources needed for their implementation have also been estimated in terms of ‘Rough Order of Magnitude’ (ROM). It should be noted that estimates should only guide planning and that for IT estimates relating to computing capacity the amounts are sufficient for pilots only. Staff estimates do not count staff already working on a process even if the process will change. The resource needs for the network are estimated for year 1 to 24 FTE, 24 in year 2 and 19 in year 3. For IT and other costs estimates are € 2.870.000 in year 1, € 3.810.000 in year 2, € 4.130.000 in year 3 not including costs for missions and meetings. The current timing is optimal for the initiative, as the new Commission is supporting digital and “EU health data space” and the EU Network Strategy to 2025 and EMA RSS to 2025 include real world data, big data and data analytics. Benefits to public health and innovation can be delivered already in year 1 and would concern the whole network. The BDTF proposed its own closure and the creation of a Big Data Steering Group to oversee among others, recommendations on implementation of key recommendations, communication advice, proposing measures to success factors, prioritising regulatory science topics and identifying funding. The endorsed


report will be published in January 2020 and a call for nominees to the Steering Group will be sent by the HMA Management Group.

A representative of patients’ organisation welcomed the report and suggested the participation of patients to the Steering Group, as they own their data. The representative of DG SANTE asked for a detailed mandate and composition document for the Steering Group in order to make sure that it would not refer to topics that are being handled in other fora. She confirmed that funding for projects may be found when it is linked to specific objectives.

B.11 HMA-EMA Task Force on the Availability of Medicines (TF AAM)

- Terms of Reference - SPOC system: report on phase 1 of the pilot - Metrics for shortages: Key information for shortage management and monitoring by EU regulators

[EMA/MB/672653/2019; EMA/857232/2016 Rev1; EMA/410297/2019; EMA/548142/2018; EMA/605066/2019] The Management Board agreed to the extension of the mandate of the TF AAM and confirmed its two Co-chairs (Kristin Raudsepp and Noel Wathion), noted the status report on the SPOC system, and adopted the Key information for shortage management and monitoring by EU regulators.

The TF AAM was established in 2016 and its 3-year mandate should now be reviewed by HMA and the Management Board. A 2018-2020 work programme was adopted in July 2018. HMA extended the mandate for a further three years (2020-2022) at its November 2019 meeting and confirmed Kristin Raudsepp as Co-chair. A number of deliverables are foreseen for 2020: the implementation of the Guidance on the detection and notification of shortages to MAHs and the Key information for shortage management and monitoring by EU regulators, as well as the Good practice guidance for EU authorities on public communication.

The metrics for shortages were developed to facilitate management and monitoring of shortages across the EU. A list of key data elements is proposed to be recorded by EU regulators as part of the shortages case management, and no additional form needs to be filled out. The list is not meant to replace the current procedures already in place at national level, however harmonisation is desirable. HMA adopted the metrics on shortages document at its November 2019 meeting.

In 2016 HMA and EMA adopted the concept of single point of contact (SPOC) together with the Terms of Reference of the TF AAM. In July 2018 HMA agreed to a proposal by the TF AAM to establish a SPOC in human and veterinary agencies that would be able to coordinate sharing of information and subsequent actions in relation to shortages and availability of authorised Medicines. The SPOC system was set up to improve collaboration across the EU regulatory network on shortages and availability issues and is designed as a single system covering Centrally Authorised Products (CAPs) and Nationally Authorised Products (NAPs) for both human and veterinary use. In its Phase I launched on 9 April 2019 and finished 15 August 2019, the process for sharing information was tested. In Phase II, scheduled to start in Q1 2020, the escalation of critical shortages to committees and pre-warning of the network of upcoming high impact public communications will be piloted. During pilot phase I the SPOC system registered 52 notifications of shortages and availability issues to be shared amongst Member States, the majority of which was for human medicines considered critical by Member States under national procedures. Root causes related to quality/manufacturing difficulties, increased


demand or commercial aspects. A survey of NCAs on workload and resources met with a high response rate and showed that medicines availability problems are widely spread in the EU but affect Member States to a different extent. Almost 70% of NCAs confirmed having between 1 and 3 FTEs working on availability issues, while most NCAs did not allocate additional staff for SPOC activities. The SPOC system is considered to be a valuable platform to exchange information and has improved collaboration. By the end of phase I, most Member States had used the SPOC system. The survey results also suggested that it would be beneficial to develop a single online repository to share information. EMA will consider this project in the context of its Work Programme 2020.

B.12 Update on preparation for implementation of Veterinary Medicinal Products Regulation (VMP-Reg)

The representative of DG SANTE updated the board on the status of the implementation. The first four EMA advice documents were received on time. The targeted stakeholder consultation was completed and has been taken into account of in the initial draft acts. Also the EMA advice on the criteria for reserving antimicrobials for treatment of certain infections in humans was received on time. Targeted stakeholder consultations have been ongoing after its publication on the implementation page. The Standing Committee on Veterinary Medicinal Products and the Veterinary Pharmaceutical Committee Expert Group met on 2 and 3 December to discuss the mandate to EMA on the list of antimicrobials not to be used under the cascade use or to be used under the cascade subject to certain conditions, the first drafts of five acts, as well as the EMA advice on the criteria for reserving antimicrobials. Written comments by Member States are expected by 17 January 2020. In 2020 EMA advice on several mandates is expected with deadlines spread during spring. A study on monographs will be launched in early 2020. Concerning resources, the European Commission is satisfied with the outcome of the 2020 Budget Procedure which has secured additional funds for € 2 million and 5 posts to reinforce and supplement the current attribution for the implementation work. 2020 will be the year with the highest workload, with different steps of procedure for the different packages running in parallel.

EMA informed the board on ongoing budget/resource discussions. Despite the additional funds and posts obtained in the final amended budget, only 1/3 of the budget required in the previously presented plans is available. Expectations for 2020 will therefore need to be adjusted, and for 2021 larger than previously presented allocation will need to be considered in order to enable delivery of all basic legislative requirements on time. Concerning the status of the programme, recommendations were delivered to the Commission on time and work on further 6 mandates is ongoing. The VMP-Reg governance endorsed in October is being established with some minor changes. EVVet3 is being re-planned due to underfunding in comparison to its business case in 2019 and 2020. For the Union Product Database (UPD) development is scheduled to begin in 2020, and prioritisation of functionalities to be delivered with a limited budget in 2020 is underway. The European Commission has indicated that it will target earlier adoption of the implementing acts to give more time to EMA to develop both UPD and EVVet3. EMA fears working on moving targets as further requirements might arise from the discussions of the implementing acts. Experience has shown that particularly for the UPD requests for functionality may still come from different expert groups working on diverse mandates. Over 2019 preparatory work for the implementation has involved an average of 7 FTE, peaking in August with 10 FTE engaged at the time when the delivery of a number of Scientific Advice was due. The workload has impacted not only on resources in the Veterinary Medicines Division, but also substantially on the Information Management Division and to a lesser extent on others. The impact of the investment made on the preparation of the implementation is being felt on other activities of the Veterinary Division such as AMR. In 2019 total hours recorded for AMR will be in line with 2017 and 2018 due to the AMR team doing overtime work to compensate for shortage of resources in the team. For the Veterinary Medicines Division total overtime amounted to 3 FTE in 2018 and had reached 2.1 FTE


equivalent in the first 10 months of 2019. With the new provisions in the veterinary medicinal products regulation, tasks in the veterinary team will expand and will require additional resources already in the preparation for the implementation phase. Next steps will be the complete establishment of the VMP-Reg governance, confirmation of budget for the 2020 programme, recruitment of the additional allocated posts, re-planning and continued delivery of EVVet3 and planning and start of delivery of UPD, as well as ongoing participation in discussion of implementing acts at the Standing Committee and commitment to deliver requested Scientific Advice on time to the Commission.

B.13 Yearly revision of the EMA Information Management Strategy and Information Management Strategic Plan

[EMA/MB/647746/2019; EMA/410709/2019; EMA/410763/2019] The Management Board noted the revised EMA Information Management Strategy 2020-2022 and the Information Management Strategic Plan 2020-2022 and postponed endorsement to a written procedure with deadline 22 January 2020.

The point was discussed in the context of B.7 Programming. Details of the discussion can be found under the above point.

B.14 Audit Strategy and Annual Audit Plan

a) Audit Strategy 2020 – 2022 [EMA/MB/615428/2019; EMA/MB/533310/2019] The Management Board adopted the Audit Strategy 2020-2022 and the Annual Audit Plan for 2020. The Audit Strategy relies on the analysis of the Agency’s risk register, applicable legal requirements, priorities laid down in the EMA Multiannual Work Plan, and takes into account the EMA BCP. The audits will be performed by AF-Audit, ECA, the IAS and external audit service providers; this will be complemented by dedicated discussion with senior management of the Agency. In 2020 it is foreseen that the Agency will be subject to 9 audits compared to 6 audits in 2019. The team of the EMA Audit Function (AF-Audit) will also conduct regular follow-up of audit recommendations, strengthen cooperation with IQM Coordinators, prepare awareness campaigns and target audit-related training, also participation in BEMA SG work in preparation of new methodologies for BEMA V.

B.15 Electronic product information (ePI): key principles and roadmap

[EMA/MB/600460/2019; EMA/240743/2019; EMA/503860/2019] The Management Board endorsed the EMA–HMA ePI roadmap and the Electronic product information for human medicines in the EU – key principles. The initiative on ePI is a joint EMA/HMA/EC collaboration which recognises other ongoing initiatives in this area and builds on a report from the European Commission on shortcomings in the Product Information issued in March 2017. ePI is defined as authorised, statutory product information for medicines in a semi-structured format created using the common EU electronic standard. ePI is adapted for electronic handling and allows dissemination via the world wide web, e-platforms and print. Its health impact is expected to be immediate and wide-reaching, to complement and enhance ongoing eHealth initiatives and has met with a broad agreement by stakeholders to progress. There is now a need to find the resources for its development, or risk loss of momentum and unharmonised development across the EU. The ePI roadmap intends to guide the implementation on the basis of key principles. According to the roadmap, an ePI set-up project, led by EMA and HMA, aims at defining a EU common standard and providing the tools needed to initiate the implementation, and is estimated


to last about 14 months. The project would be followed by a pilot phase by EMA and interested NCAs. After the endorsement by EMA and HMA, the ePI key principles will be published on the respective websites in Q1 2020. The funding options for the ePI set-up project will need to be explored, as there are currently none available within the EMA budget.

B.16 EMA implementation of medical devices and in-vitro diagnostic regulations

The representative of DG GROW updated the board on the state of play concerning the implementation of the new EU Regulations on medical devices. As a practical consequence of the publication of a corrigendum on 3 May 2019 more time will be granted for Class I device manufacturers to prepare, and this should alleviate the pressure on Notified bodies. The availability of Notified Bodies is improving, as 10 very large ones have completed their designation procedure and more are in the pipeline. The European Commission has confirmed that the EUDAMED database will not be available in 2020 but rather in 2022, which is an option foreseen in the legislation. A module for voluntary registration will however already be made available in 2020. Concerning Brexit, the transfer of Notified bodies to the EU is taking place smoothly. The Medical Devices Regulation covers a wide range of devices, of which some are very close to medicinal products. Specific coordination between EMA and the European Commission will be required to assure arbitration in borderline cases.

EMA informed the board about how the Agency is preparing for the parts of the regulations that will affect it. Five areas for implementation of the Medical Devices Regulations are relevant for EMA: devices with ancillary medicinal substances, devices composed of substances that are systemically absorbed, borderline products, medicinal products incorporating an integral medical device and finally companion diagnostics. Collaboration between all parties involved (Commission, CMDh, Joint HMA-CAMD groups, Notified bodies etc.) is key. Q&As, as well as several pieces of guidance on practical implementation, have been published and a final QWP/BWP scientific guideline is expected to be published by Q2 2020. When article 117 of the MDR enters into force on 26 May 2020, Notified bodies will need to be consulted on general safety and performance requirements before adoption of a CHMP opinion. Should there not be enough Notified bodies, an impact on new medicinal products availability could be feared. CAPs could be affected, as in 2020 ca 25 new applications are expected to contain an integral device, and some of the over 100 existing CAPs with devices could be impacted as well. On 31 March 2020 EMA is organising a 1 Day Workshop on Article 117 to make sure that device and medicines regulators understand the changes in requirements for MAA of single integral products when the MDR enters into force on 26 May 2020. The EMA has prepared proposals for fees for new EMA consultations on medical devices concerning substance based-medical devices and companion diagnostics. The proposals will be presented as amendments to the fee implementing rules at the meeting of the Management Board in March 2020. The proposals were prepared using the ancillary substance procedures as benchmark. Borderline products will produce a blurring of applicable frameworks and pose a technological challenge in healthcare for which regulators need to be ready. Within the new legislation the European Commission can consult EMA when deliberating the status of products on the borderline with medicines. A stakeholder consultation workshop confirmed the need to create and integrated evaluation pathways for the assessment of medical devices, in vitro diagnostics and borderline products. To this purpose it will be necessary to establish stronger ties with device authorities and develop specific expertise.

A member reminded the board that there is still much work to be done in the five months to the May 2020 deadline, and expressed concern that MedTech companies seem to be moving out of the EU due to uncertainty. Gratitude was expressed for the work of the European Commission’s Medical Devices Coordination Group but capacity issues remain. EUDAMED is fundamental for the implementation of


the system, and if all Member States start developing their part there will not be the required cohesion.

B.17 Annual report on the implementation of the EMA’s Anti-Fraud Strategy

On 29 April 2019 the Commission’s Anti-Fraud strategy and related Action Plan were approved. The Management Board had adopted the revised Anti-Fraud Strategy and Action Plan for 2018-2020 at its meeting of December 2017. The two actions to be performed on an annual basis, assessing adequacy and effectiveness of the controls in place, and conducting fraud-specific risk assessments, have been regularly implemented. The revised strategy of 2017 foresaw performing proactive random verifications in cooperation with the relevant Head of Division. Due to the BCP context and the relocation in 2019, it was considered that proactive random verifications would have interfered with priority activities in the BCP programme. The action will be carried over and is likely to be resumed in 2020. In 2019 EMA had no cases notified to OLAF and received only one internal reporting about allegedly fraudulent behaviours, then revealed prima facie inconsistent. Training activities for new staff and contractors will continue.

B.18 Report on the implementation by EMA of the EU Data Protection Regulation (EUDPR)

EUDPR entered into force on 11 December 2018 and is applicable to Union institutions, bodies, offices and agencies when processing personal data in relation with their core tasks or operational activities. To achieve a basic level of compliance a number of measures were taken at the Agency, such as preparing and publishing internal rules on Article 25 restrictions, Implementing Rules concerning the Data Protection Officer, conducting an IT security review, updating the records of processing activities and introducing new clauses in procurement procedures. The central register of data processing activities will be published on the Agency’s website in 2020, and the establishment of a Personal Data Breach Management Procedure and of the Data Breach Register were implemented. Data Protection Impact Assessments were introduced as a new obligation for data controllers and the first one on the new clinical trial data base is being drafted. Training modules for all staff were developed and will become mandatory for newcomers, together with specific training sessions for colleagues involved for. Ex. in procurement procedures. Ongoing measures to enhance compliance include identifying legal obligations/public interest tasks of EMA as legal basis of data processing, introducing data processing by design in all technology selection processes, development of formal data protection SOP and template instruments for international data transfers. The implementation of the EDPR is a massive exercise that was required the work of 3.8 FTE in 2019. These mandatory activities are more resource-intensive than anticipated at the time of their adoption by the co-legislator. Staffing the Agency adequately to cope with these tasks represents another serious challenge that will need to be carefully analysed next year.

B.19 Management of Nitrosamine presence in medicines

Susanne Keitel, Director of EDQM, and Laura Oliveira Santamaria, Chair of CMDh, joined the meeting for the discussion of this topic.

[EMA/MB/687292/2019; EMA/MB/678452/2019] The Management Board endorsed the Handling of new information on nitrosamine presence in medicines, laying down an EU regulatory network short-term and temporary approach. The Agency reminded the board of the events that had taken place from the European Commission Decision for sartans containing a tetrazole group issued on 2 April 2019, to the


start in September 2019 of an Art. 31 referral for ranitidine containing medicines, and of an Art 5(3) referral for human medicines containing chemically synthesised APIs, the subsequent launch of call for review to MAHs in the frame of the Art 5 (3) procedure, the agreement by the EU Regulatory Network during a teleconference on 25 September 2019 on how to operate the overall process within the 3 year timeframe, up to the meeting on 4 November on the sartans lessons learnt exercise (LLE) in which interested parties discussed how to better prevent and manage cases of medicines with nitrosamine impurities in the future. Continued discussions have been going on at CHMP and CMDh in Q4, and the CVMP agreed at its December meeting to look into the need for a similar approach for veterinary medicinal products. HMA agreed at its 28 November meeting on an EMA proposal for further action. Already planned next steps include continuation of the two referral procedures in Q1 2020, the finalisation and subsequent publication of the sartans LLE report in Q1 2020, and continuation of international collaboration, including discussion on the need for revision of the ICH M7 guideline on genotoxic impurities. Nitrosamine presence is a complex public health issue with the potential for shortages of medicines. Scientific knowledge is developing on a daily basis, and unprecedented organisational and operational challenges need to be addressed, including capacity problems at EMA, within the EU Regulatory Network, for international partners and for the pharmaceutical industry. Further action will need to be based on agreement by EU Regulatory Authorities from a holistic public health point of view on the risk acceptance towards the presence of nitrosamines in medicinal products, alignment with the positions taken by other regulators in an effort at inter-regional convergence, agreement on the best way to interact with pharmaceutical industry and timing of communication at the various milestones of the process, ensuring the use of existing crisis management procedures and structures in case of need, and finally avoidance of ‘mini’ crisis situations impacting on the ability to cope with such situations, for as long as the CHMP has not yet concluded its risk assessment in the context of the Article 5(3) review. Waiting the outcome of the CHMP discussions under the Article 5(3) referral some immediate actions were proposed to deal with emerging information on nitrosamine presence. They were discussed at the December CHMP and CMDh meetings and endorsed. Comments made during the discussions and subsequent feedback received from the Commission were taken into account. The current handling of new cases of nitrosamine presence follows the established process, but there is an increasing risk that while the CHMP review is ongoing any emerging information may lead to inconsistent action. A short term and temporary solution for the EU regulatory network was proposed, whereby any new information will continue to be circulated using the existing Rapid Alert Network (RAN), and interim limits agreed by the CHMP in the context of the sartans referral on a temporary basis until April 2021 will be used, as well as the interim limits subsequently agreed based on the Safety Working Party opinion for other nitrosamine impurities. If for any new cases of nitrosamine detection in a medicine these interim limits are not exceeded, competent authorities should be informed on the levels of impurities detected. Should the interim limit be exceeded, the MAH(s) concerned should immediately calculate the adjusted interim limit taking into account the duration of the treatment for the particular medicine and inform the NCAs. Should the adjusted interim limit be exceeded, , the Incident Review Network (IRN) should be convened to discuss and agree the best way forward. This interim solution will not affect MAHs’ activities to be undertaken as per the steps described in the Information Note published in September 2019. The updated Q&A would reflect the interim solution and would be published on the EMA/HMA/CMDh websites, with a request for Member States to cascade this information on their national websites and to EU industry trade associations for dissemination to their national member associations. In order to ensure availability of sufficient capacity in terms of testing, acknowledging current existing capacity problems at the level of OMCLs, it was proposed to map current and planned testing undertaken by EU OMCLs, sharing of information between all international regulators in view of subsequently undertaking a mapping, and identifying spare capacity and agree on a testing strategy.


Members of the board acknowledged the swift response of the Agency. In the discussion it was suggested that GMP inspection standards could be further adapted based on experience, and also pay particular attention to APIs and excipients. MAHs should be asked to conduct periodic risk assessments on their supply chains. Coordination of testing was considered essential to share the workload as much as possible, while national action without discussion within IRN could lead to inconsistent actions. The Chair of CMDh informed the board that the proposal presented by the Deputy Executive Director of EMA was the result of discussion that had included CMDh, and that it would provide needed coordination between CAPs and NAPs. The representative of DG SANTE thanked EMA for the initiative, which provides a good interim solution, and reminded the board of the responsibilities of the MAHs and of the competent authorities, which might in certain cases need to take some action to manage risks. If the European Commission and Member States consider to have reasons for action, they should inform the network so that EMA can convene the appropriate structures. Concerning international coordination, EMA informed that the issue is global and exchanges take place regularly in teleconferences with EDQM, non-EU regulatory authorities, and with EMA rapporteurs. There is awareness of actions taken, and a number of international partners follow the same approach as the EU concerning interim limitsInternational partners are interested in the work of the ad-hoc expert group which will meet in the context of the Art 5(3) referral and in the testing strategies to avoid duplication. In response to questions about the current status of the LLE (lessons learnt experience) for sartans, the Deputy Executive Director replied that the LLE report, hopefully to be presented at the March meetings of HMA and of the Management Board, will include recommendations addressing also communication and GMP inspection aspects.

The Director of EDQM informed the board on the current status of nitrosamine testing in the OMCL network. She reminded the board that testing poses analytical challenges, as the quantity of ‘usual’ impurities to be detected normally is in the environ of 1 ml in a 1L solution (1000 ppm), while for nitrosamine it is 1ml in a 33’000L solution (0.03ppm or 30 ppb). 13 EU OMCL as well as associate members from Canada and Singapore were initially involved in testing for nitrosamine in sartans, which have 0.300 ppm interim limit for NDMA. The two successive substances to be tested, ranitidine and metformine, have tighter interim limits, and the number of OMCLs as well as associate members able to test them is decreasing, as not all have the necessary equipment. Three OMCLs have indicated that they will start procuring additional instruments, but it must currently be assumed that participation will be limited to a certain number of laboratories for which the capacity will largely depend on the priorities given for this work by their national authorities. Lack of suitable instrumentation is not the only obstacle for OMCLs, as each new molecule requires substance or drug product specific validation implying time, resource and samples, and laboratory capacity is used also for routine national or CAP testing programmes or the OMCL is still working on sartan and ranitidine samples. Sampling is normally triggered by the national inspectorates and is not coordinated across Member States. Concerning metformine, optimisation and coordination of planning and sampling is needed. For other APIs in 2020-2021 the prospective plan is for OMCLs to work towards interim limits similar to the sartan phase 1 and to focus on NDMA and NDEA for screening. A meaningful priority list for APIs potentially at risk should be established using information sourced from MAH reviews and literature as well as feedback from GMP inspections and previous incidents at the site. Coordination of the OMCL work can be initiated on the basis of existing screening and testing programmes.

A question was asked as to the remuneration of testing performed by OMCLs. These are currently not payed. The Deputy Executive Director pointed out that there is a risk that all OMCLs test the same substance when new information emerges, until a problem with another substance appears. Questions arise as to what data are needed to take regulatory action, whether they should come from testing, and what kind of testing is needed. The Director of EDQM concluded that testing is based on a mutual quality system, and that therefore a platform to collect the data on a single IT platform is needed.


Improvements are needed to enable timely identification of the source of API. She encouraged NCAs to reflect on whether an increase of resources is needed in their own OMCL.


List of written procedures finalised during the period from 17 September 2019 to 22 November 2019

• Consultation no 15/2019 on the appointment of Nijolė Stankevičienė CVMP alternate as proposed by Lithuania ended on 30 October 2019. The mandate of the nominee commenced on 31 October 2019.

• Consultation no 16/2019 on the appointment of Miguel Escribano as CVMP member as proposed by the United Kingdom ended on 15 November 2019. The mandate of the nominee commenced on 16 November 2019.

• Consultation procedure for endorsement of the HMA-EMA Joint Big Data taskforce subgroup reports from Phase I for endorsement for external publication ended on 21 October 2019.

• Consultation procedure for information concerning the permanent EMA building in Amsterdam. The procedure was launched on 8 November 2019.

• Consultation procedure for information concerning the permanent EMA building in Amsterdam. The procedure was launched on 14 November 2019.

Documents for information

• [EMA/MB/578488/2019; EMA/578489/2019] Report on EU Telematics

• [EXT/682256/2019] Feedback from the Heads of Medicines Agencies

• [EMA/MB/638477/2019] Outcome of written procedures finalised during the period from 17 September 2019 to 22 November 2019

• [EMA/MB/582178/2019] Summary of the transfers of appropriation 2019 and Summary report on implementation of assigned revenue

• [EMA/MB/596721/2019; EMA/596711/2019] Revised Executive Directors decision on rules governing tuition fees for dependents of secondment of national experts to the EMA

• [EMA/MB/651058/2019; EMA/654264/2019 Rev.4] European Ombudsman’s (EO) decision on pre-submission activities; update of the Procedural Advice on the CHMP/CAT/PRAC (Co)-Rapporteur appointment


List of participants at the 106th meeting of the Management Board, held in Amsterdam, 18-19 December 2019

Chair: Christa Wirthumer-Hoche

Participants Belgium Xavier De Cuyper (member) Bulgaria Apology received from Bogdan Kirilov (member) Czech Republic Irena Storová (member) Croatia Siniša Tomić (alternate) Denmark Thomas Senderovitz (member)

Mette Aaboe Hansen (alternate) Tina Engraff (observer)

Germany Lars Nickel (alternate) Wiebke Loebker (observer)

Estonia Apology received from Kristin Raudsepp (member)

Ireland Lorraine Nolan (member) Rita Purcell (alternate)

Greece Eleftherios Pallis (member) 1 Spain María Jesús Lamas Diaz (member)

César Hernández (alternate) María Jesús Alcaraz Tomas (observer)

France Jean-Pierre Orand (alternate) Miguel Bley (observer)

Italy Anna Laura Salvati (observer) Cyprus Loizos Panayi (member) Latvia Svens Henkuzens (member) Lithuania Gytis Andrulionis (member) Luxembourg Laurent Mertz (member) Hungary Mátyás Szentiványi (member) 1

Malta Anthony Serracino-Inglott (member) John-Joseph Borg (alternate)

Netherlands Hugo Hurts (member) Michiel Hendrix (observer)

Austria Thomas Reichhart (alternate) Poland Grzegorz Cessak (member)

Marcin Kolakowski (alternate) Portugal Rui Santos Ivo (member)

Maria Morais (observer) Romania Marius Șișu (member) 1 Slovakia Zuzana Baťová (member) Slovenia Momir Radulović (member) 1 Finland Esa Heinonen (alternate) Sweden Catarina Andersson Forsman (member)

Evelina Kaarme (observer) 1 Competing interest declared resulting in no participation in decision with respect to agenda points B.7, B.8.b), B.11, B.13, B.15 and B.19. .


United Kingdom Jonathan Mogford (alternate)

European Parliament

Matthias Groote Tonio Borg

European Commission Anne Bucher (DG SANTE) Carlo Pettinelli (DG GROW) Aude L’hirondel DG SANTE (observer) Laura Fabrizi DG GROW (observer)

Representatives of patients' organisations Ioannis Natsis Marco Greco

Representative of doctors' organisations Wolf Dieter Ludwig Representative of veterinarians' organisations Nancy de Briyne Observers Runa Hauksdottir Hvannberg (Iceland)

Apology received from Martin Stricker (Liechtenstein) Audun Hågå (Norway)

Delegation present during point B.10 Nikolai Constantin Brun, Chair Joint HMA-EMA Task Force on Big Data

Delegation present during point B.19 Dr Susanne Keitel, Director of EDQM Laura Oliveira Santamaria, Chair of CMDh

European Medicines Agency Guido Rasi Noël Wathion Nerimantas Steikūnas Agnes Saint-Raymond Alexis Nolte Fergus Sweeney Zaide Frias Ivo Claassen Melanie Carr Anthony Humphreys Peter Arlett Edit Weidlich Stefano Marino Christine Bugge Michael Lenihan Monica Dias Mario Benetti Marie-Agnes Heine Rebecca Harding Hilde Boone Frances Nuttall Maria Alves Silvia Fabiani Apolline Lambert Sophia Albuquerque